Cited by 184Telomeres, Telomerase, and SenescenceRetinal Diseases and TreatmentsAngiogenesis and VEGF in Cancer

The DOI matches its Crossref record; 81 of the 81 references it cites were found in a registry or an index.

Pathological angiogenesis in retinopathy engages cellular senescence and is amenable to therapeutic elimination via BCL-xL inhibition

Open access

Crespo-Garcia, Sergio, Tsuruda, Pamela R., Dejda, Agnieszka, Ryan, Rathi D., Fournier, Frederik, Chaney, Shawnta Y., Pilon, Frederique, Dogan, Taner, Cagnone, Gael, Patel, Priyanka, Buscarlet, Manuel, Dasgupta, Sonali, Girouard, Gabrielle, Rao, Surabhi R., Wilson, Ariel M., O’Brien, Robert, Juneau, Rachel, Guber, Vera, Dubrac, Alexandre, Beausejour, Christian, Armstrong, Scott, Mallette, Frederick A., Yohn, Christopher B., Joyal, Jean-Sebastien, Marquess, Dan, Beltran, Pedro J., Sapieha, Przemyslaw·2021·Cell Metabolism

DOI 10.1016/j.cmet.2021.01.011

Open this paper in CoChat — free account Open PDF

Abstract

Attenuating pathological angiogenesis in diseases characterized by neovascularization such as diabetic retinopathy has transformed standards of care. Yet little is known about the molecular signatures discriminating physiological blood vessels from their diseased counterparts, leading to off-target effects of therapy. We demonstrate that in contrast to healthy blood vessels, pathological vessels engage pathways of cellular senescence. Senescent (p16 INK4A-expressing) cells accumulate in retinas of patients with diabetic retinopathy and during peak destructive neovascularization in a mouse model of retinopathy. Using either genetic approaches that clear p16 INK4A-expressing cells or small molecule inhibitors of the anti-apoptotic protein BCL-xL, we show that senolysis suppresses pathological angiogenesis. Single-cell analysis revealed that subsets of endothelial cells with senescence signatures and expressing Col1a1 are no longer detected in BCL-xL-inhibitor-treated retinas, yielding a retina conducive to physiological vascular repair. These findings provide mechanistic evidence supporting the development of BCL-xL inhibitors as potential treatments for neovascular retinal disease.

Integrity signals

Registry

Crossref · 10.1016/j.cmet.2021.01.011

Cites

81 of 81 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

<tt>edgeR</tt> : a Bioconductor package for differential expression analysis of digital gene expression data
Robinson, M. D., McCarthy, D. J., & Smyth, G. K. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp616 · Cited by 41,364
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453
GSVA: gene set variation analysis for microarray and RNA-Seq data
Hänzelmann, S., Castelo, R., & Guinney, J. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-7 · Cited by 15,440
Near-optimal probabilistic RNA-seq quantification
Bray, N. L., Pimentel, H., Melsted, P., & Pachter, L. (2016) · Nature Biotechnology · doi:10.1038/nbt.3519 · Cited by 9,723
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets.
Macosko, E. Z., Basu, A., Satija, R., Nemesh, J., Shekhar, K., Goldman, M., Tirosh, I., Bialas, A. R., Kamitaki, N., Martersteck, E. M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.05.002 · Cited by 7,110
Diabetic Retinopathy
Lang, G. E., Vaiser, A., Snyder, W. B., & Lynn, J. R. (2007) · Developments in ophthalmology · doi:10.1159/isbn.978-3-318-01439-6 · Cited by 5,607
Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis
Wong, W. L., Su, X., Li, X., Cheung, C. M. G., Klein, R., Cheng, C., & Wong, T. Y. (2014) · The Lancet Global Health · doi:10.1016/s2214-109x(13)70145-1 · Cited by 5,545
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H., Treacy, D., Trombetta, J. J., Rotem, A., Rodman, C., Lian, C., Murphy, G., et al. (2016) · Science · doi:10.1126/science.aad0501 · Cited by 4,944
Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression
Hafemeister, C., & Satija, R. (2019) · Genome Biology · doi:10.1186/s13059-019-1874-1 · Cited by 4,479

Show all 81 references

Sorted by citations

Cellular senescence and senolytics: the path to the clinic
Chaib, S., Tchkonia, T., & Kirkland, J. L. (2022) · Nature Medicine · doi:10.1038/s41591-022-01923-y · Cited by 1,134
The metabolic roots of senescence: mechanisms and opportunities for intervention
Wiley, C. D., & Campisi, J. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00483-8 · Cited by 691
Mechanisms and consequences of endothelial cell senescence
Bloom, S. I., Islam, M. T., Lesniewski, L. A., & Donato, A. J. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00739-0 · Cited by 521
Apoptotic cell death in disease—Current understanding of the NCCD 2023
Vitale, I., Pietrocola, F., Guilbaud, E., Aaronson, S. A., Abrams, J., Adam, D., Agostini, M., Agostinis, P., Alnemri, E. S., Altucci, L., et al. (2023) · Cell Death and Differentiation · doi:10.1038/s41418-023-01153-w · Cited by 352
Targeting angiogenesis in oncology, ophthalmology and beyond
Cao, Y., Langer, R., & Ferrara, N. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00671-z · Cited by 339
The heterogeneity of cellular senescence: insights at the single-cell level
Cohn, R. L., Gasek, N. S., Kuchel, G. A., & Xu, M. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2022.04.011 · Cited by 294
Senescence as a therapeutic target in cancer and age-related diseases
McHugh, D., Durán, I., & Gil, J. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-01074-4 · Cited by 197
Cellular Senescence in Cardiovascular Diseases: A Systematic Review
Hu, C., Zhang, X., Teng, T., Ma, Z., & Tang, Q. (2022) · Aging and Disease · doi:10.14336/ad.2021.0927 · Cited by 184
Role of Cellular Senescence in Type II Diabetes
Narasimhan, A., Flores, R. R., Robbins, P. D., & Niedernhofer, L. J. (2021) · Endocrinology · doi:10.1210/endocr/bqab136 · Cited by 133
Role of hypoxia in cellular senescence
Gao, H., Nepovimová, E., Heger, Z., Valko, M., Wu, Q., Kuča, K., & Adam, V. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106841 · Cited by 137
New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death
Bu, L.-L., Yuan, H., Xie, L., Guo, M.-H., Liao, D., & Zheng, X. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242015160 · Cited by 133
Angiogenesis in adipose tissue and obesity
Corvera, S., Solivan-Rivera, J., & Yang, Z. (2022) · Angiogenesis · doi:10.1007/s10456-022-09848-3 · Cited by 137
Senescent Cells: A Therapeutic Target in Cardiovascular Diseases
Suda, M., Paul, K. H., Minamino, T., Miller, J. D., Lerman, A., Ellison, G. M., Tchkonia, T., & Kirkland, J. L. (2023) · Cells · doi:10.3390/cells12091296 · Cited by 119
Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results
Crespo‐Garcia, S., Fournier, F., Diaz-Marin, R., Klier, S. M., Ragusa, D., Masaki, L., Cagnone, G., Blot, G., Hafiane, I., Dejda, A., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-02802-4 · Cited by 110
Self-citation
Diabetic retinopathy: Involved cells, biomarkers, and treatments
Ren, J., Zhang, S., Pan, Y., Jin, M., Li, J., Luo, Y., Sun, X., & Li, G. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.953691 · Cited by 100
Activated cGAS/STING signaling elicits endothelial cell senescence in early diabetic retinopathy
Liu, H., Ghosh, S., Vaidya, T. A., Bammidi, S., Huang, C., Shang, P., Nair, A. P., Chowdhury, O., Stepicheva, N. A., Strizhakova, A., et al. (2023) · JCI Insight · doi:10.1172/jci.insight.168945 · Cited by 102
Deciphering endothelial heterogeneity in health and disease at single-cell resolution: progress and perspectives
Becker, L. M., Chen, S.-H., Rodor, J., de Rooij, L. P. M. H., Baker, A. H., & Carmeliet, P. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac018 · Cited by 81
Recent advances in the treatment and delivery system of diabetic retinopathy
Wang, Z., Zhang, N., Lin, P., Xing, Y., & Yang, N. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1347864 · Cited by 73
Enhancement of glycolysis-dependent DNA repair regulated by FOXO1 knockdown via PFKFB3 attenuates hyperglycemia-induced endothelial oxidative stress injury
Sun, D., Chen, S., Li, S., Wang, N., Zhang, S., Xu, L., Zhu, S., Li, H., Gu, Q., Xu, X., et al. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102589 · Cited by 71
Mitochondria-targeted nanozymes eliminate oxidative damage in retinal neovascularization disease
Bai, X., Ge, M., Fan, K., Huang, X., Yan, X., Jiang, W., Jiang, B., & Yang, Z. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.08.026 · Cited by 63
Oxidative Stress-Induced Cellular Senescence in Aging Retina and Age-Related Macular Degeneration
Terao, R., Ahmed, T., Suzumura, A., & Terasaki, H. (2022) · Antioxidants · doi:10.3390/antiox11112189 · Cited by 62
The challenge of identifying senescent cells
Gil, J. (2023) · Nature Cell Biology · doi:10.1038/s41556-023-01267-w · Cited by 58
LXR/CD38 activation drives cholesterol-induced macrophage senescence and neurodegeneration via NAD+ depletion
Terao, R., Lee, T. J., Colasanti, J. J., Pfeifer, C. W., Lin, J. B., Santeford, A. C., Hase, K., Yamaguchi, S., Du, D., Sohn, B. S., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114102 · Cited by 62
Vascular Endothelial Senescence: Pathobiological Insights, Emerging Long Noncoding RNA Targets, Challenges and Therapeutic Opportunities
Sun, X., & Feinberg, M. W. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.693067 · Cited by 56
Long term high glucose exposure induces premature senescence in retinal endothelial cells
Bertelli, P. M., Pedrini, E., Hughes, D. W., McDonnell, S., Pathak, V., Peixoto, E., Guduric‐Fuchs, J., Stitt, A. W., & Medina, R. J. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.929118 · Cited by 57
Pathophysiology of Retinopathy of Prematurity
Hartnett, M. E. (2023) · Annual Review of Vision Science · doi:10.1146/annurev-vision-093022-021420 · Cited by 56
Senescent-like macrophages mediate angiogenesis for endplate sclerosis via IL-10 secretion in male mice
Fan, Y., Zhang, W., Huang, X., Fan, M., Shi, C., Zhao, L., Pi, G., Zhang, H., & Ni, S. (2024) · Nature Communications · doi:10.1038/s41467-024-47317-1 · Cited by 47
CD44 connects autophagy decline and ageing in the vascular endothelium
Zhang, L., Yang, P., Chen, J., Chen, Z., Liu, Z., Feng, G., Sha, F., Li, Z., Xu, Z., Huang, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41346-y · Cited by 45
Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling
He, X., Wen, S., Tang, X., Wen, Z., Zhang, R. H., Li, S., Gao, R. B., Wang, J., Zhu, Y., Fang, D., et al. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.03.011 · Cited by 47
Senolytic and senomorphic agent procyanidin C1 alleviates structural and functional decline in the aged retina
Liu, Y., Liu, X., Chen, X., Yang, Z., Chen, J., Zhu, W., Li, Y., Wen, Y., Deng, C., Gu, C., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2311028121 · Cited by 43
Mechanisms of RPE senescence and potential role of αB crystallin peptide as a senolytic agent in experimental AMD
Sreekumar, P. G., Reddy, S. T., Hinton, D. R., & Kannan, R. (2022) · Experimental Eye Research · doi:10.1016/j.exer.2021.108918 · Cited by 42
Senescent cells at the crossroads of aging, disease, and tissue homeostasis
Kuehnemann, C., & Wiley, C. D. (2023) · Aging Cell · doi:10.1111/acel.13988 · Cited by 44
Senescent endothelial cells: a potential target for diabetic retinopathy
Liao, Y.-L., Fang, Y., Sun, J., & Dou, G. (2024) · Angiogenesis · doi:10.1007/s10456-024-09943-7 · Cited by 40
Senolytics in the treatment of diabetic retinopathy
Hassan, J. W., & Bhatwadekar, A. D. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.896907 · Cited by 39
Death-seq identifies regulators of cell death and senolytic therapies
Colville, A., Liu, J., Rodríguez-Mateo, C., Thomas, S. M., Ishak, H. D., Zhou, R., Klein, J. D. D., Morgens, D. W., Goshayeshi, A., Salvi, J. S., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.08.008 · Cited by 36
Potential Clinical Implications of Senotherapies for Cardiovascular Disease
Suda, M., Katsuumi, G., Tchkonia, T., Kirkland, J. L., & Minamino, T. (2023) · Circulation Journal · doi:10.1253/circj.cj-23-0657 · Cited by 37
Impaired Remodeling of White Adipose Tissue in Obesity and Aging: From Defective Adipogenesis to Adipose Organ Dysfunction
Iacobini, C., Vitale, M., Haxhi, J., Menini, S., & Pugliese, G. (2024) · Cells · doi:10.3390/cells13090763 · Cited by 42
Hyperlipidemia induces proinflammatory responses by activating STING pathway through IRE1α-XBP1 in retinal endothelial cells
Wen, Z., He, X., Wang, J., Wang, H., Li, T., Wen, S., Ren, Z., Cai, N., Yang, J., Li, M., et al. (2022) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2022.109213 · Cited by 34
The Bcl-2/Bcl-xL Inhibitor ABT-263 Attenuates Retinal Degeneration by Selectively Inducing Apoptosis in Senescent Retinal Pigment Epithelial Cells
Ryu, W., Park, C.-W., Kim, J., Lee, H., & Chung, H. (2023) · Molecules and Cells · doi:10.14348/molcells.2023.2188 · Cited by 34
Mesenchymal stem cells-derived exosomes alleviate senescence of retinal pigment epithelial cells by activating PI3K/AKT-Nrf2 signaling pathway in early diabetic retinopathy
Bai, L., & Wang, Y. (2024) · Experimental Cell Research · doi:10.1016/j.yexcr.2024.114170 · Cited by 32
Immune response in retinal degenerative diseases – Time to rethink?
Xu, H., & Chen, M. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102350 · Cited by 33
A nutrigeroscience approach: Dietary macronutrients and cellular senescence
Calubag, M. F., Robbins, P. D., & Lamming, D. W. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.07.025 · Cited by 33
Single‐cell RNA sequencing in exploring the pathogenesis of diabetic retinopathy
Zhang, X. Y., Zhang, F., & Xu, X. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.1751 · Cited by 30
Beyond the Complement Cascade: Insights into Systemic Immunosenescence and Inflammaging in Age-Related Macular Degeneration and Current Barriers to Treatment
Khan, A. H., Chowers, I., & Lotery, A. J. (2023) · Cells · doi:10.3390/cells12131708 · Cited by 31
Retinopathy of prematurity: Metabolic risk factors
Fu, Z., Nilsson, A., Hellström, A., & Smith, L. E. H. (2022) · eLife · doi:10.7554/elife.80550 · Cited by 30
α-Klotho prevents diabetic retinopathy by reversing the senescence of macrophages
Li, Q., Wang, P., Xu, M., Gong, Y., Wang, M., Luan, R., Liu, J., Li, X., Li, X., & Shao, Y. X. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01838-w · Cited by 31
Cellular senescence primes liver fibrosis regression through Notch‐EZH2
Song, P., Duan, J., Ding, J. H., Liu, J., Fang, Z., Xu, H., Li, Z., Du, W., Xu, M., Ling, Y., et al. (2023) · MedComm · doi:10.1002/mco2.346 · Cited by 25
Safety and Efficacy of Senolytic UBX1325 in Diabetic Macular Edema
Klier, S. M., Dananberg, J., Masaki, L., Bhisitkul, R. B., Khanani, A. M., Maturi, R. K., Salehi-Had, H., Mallinckrodt, C. H., Rathmell, J. M., Ghosh, A., et al. (2025) · NEJM Evidence · doi:10.1056/evidoa2400009 · Cited by 27
Self-citation
UCP2–SIRT3 Signaling Relieved Hyperglycemia-Induced Oxidative Stress and Senescence in Diabetic Retinopathy
Li, S., Sun, D., Chen, S., Zhang, S., Gu, Q., Shen, Y., Li, X., Xu, X., Wei, F., & Wang, N. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.1.14 · Cited by 27
A new clinical age of aging research
Zhang, Z., Yang, R., Zi, Z., & Liu, B. (2024) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2024.08.004 · Cited by 25
Mesenchymal Stem Cell-Derived Mitochondrial Transfer Promotes Tip Cell Phenotype via Glutathione Metabolic Reprogramming in Stroke Mice
Zhang, Q., Huang, J., Chen, X., Li, L., Chen, L., Zhou, X., Zhao, X., Liu, M., Zhao, W., Yan, J., et al. (2025) · ACS Nano · doi:10.1021/acsnano.4c15759 · Cited by 25
Adipose tissue aging: An update on mechanisms and therapeutic strategies
Cai, Z., & He, B. (2022) · Metabolism · doi:10.1016/j.metabol.2022.155328 · Cited by 27
Innate immunity dysregulation in aging eye and therapeutic interventions
Das, S., Ahmad, Z., Suryawanshi, A. S., & Kumar, A. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101768 · Cited by 24
Obesity triggers tumoral senescence and renders poorly immunogenic malignancies amenable to senolysis
Fournier, F., Diaz-Marin, R., Pilon, F., Neault, M., Juneau, R., Girouard, G., Wilson, A. M., Larrivée, B., Mallette, F. A., Crespo‐Garcia, S., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2209973120 · Cited by 23
Self-citation
Natural killer cells promote neutrophil extracellular traps and restrain macular degeneration in mice
Dong, X., Song, Y., Liu, Y., Kou, X., Yang, T., Shi, S. X.-Y., He, K., Li, Y., Li, Z., Yao, X., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adi6626 · Cited by 22
Recent developments of neuroprotective agents for degenerative retinal disorders
Wu, J., Ou, K., Li, Y., Liu, L., Li, H., Cox, K. H. M., Liu, J., & Dick, A. D. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.335140 · Cited by 23
The role of cellular senescence in metabolic diseases and the potential for senotherapeutic interventions
Zhang, H., Zhou, H., Shen, X. M., Lin, X., Zhang, Y., Sun, Y., Zhou, Y., Zhang, L., & Zhang, D. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1276707 · Cited by 25
The Role of Senescence-Associated Secretory Phenotype in Bone Loss
Zhu, R., Wan, H., Yang, H. S., Song, M., Chai, Y., & Yu, B. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.841612 · Cited by 21
Revisiting Retinal Degeneration Hallmarks: Insights from Molecular Markers and Therapy Perspectives
da Rosa, J. G. S., Disner, G. R., Pinto, F. J., Lima, C., & Lopes‐Ferreira, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713079 · Cited by 23
Age-Related Macular Degeneration: A Disease of Cellular Senescence and Dysregulated Immune Homeostasis
Li, C., Zhou, L., Sun, H., & Yang, M. S. (2024) · Clinical Interventions in Aging · doi:10.2147/cia.s463297 · Cited by 21
Obesity drives depot-specific vascular remodeling in male white adipose tissue
Hasan, S. S., John, D., Rudnicki, M., AlZaim, I., Eberhard, D., Moll, I., Taylor, J., Klein, C., von Heesen, M., Conradi, L., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60910-2 · Cited by 20
Deletion of METTL14, a key methylation regulator, attenuates vascular ageing
Liu, X., Liu, H., Lin, Y., Lou, H., Feng, J., Sun, X., Wang, J., Dong, X., Liu, L., Sun, Z., et al. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf476 · Cited by 19
Mechanical stimuli-induced CCL2 restores adult mouse cells to regenerate hair follicles
Wu, W., Zhou, W., Jiang, J., Wang, M., Zhang, J., Yang, J., Tang, Q., Liu, H., Liu, D., Xu, W., et al. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.03.002 · Cited by 21
Cellular senescence as a key contributor to secondary neurodegeneration in traumatic brain injury and stroke
Huang, Z., Xu, P., Hess, D. C., & Zhang, Q. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00457-2 · Cited by 20
Cellular Senescence: A Bridge Between Diabetes and Microangiopathy
Liu, J., Guo, B., Liu, Q., Zhu, G., Wang, Y., Wang, N., Yang, Y., & Fu, S. (2024) · Biomolecules · doi:10.3390/biom14111361 · Cited by 21
Does senescence play a role in age-related macular degeneration?
Malek, G., Campisi, J., Kitazawa, K., Webster, C. M., Lakkaraju, A., & Skowronska‐Krawczyk, D. (2022) · Experimental Eye Research · doi:10.1016/j.exer.2022.109254 · Cited by 18
Lycopene Improves Bone Quality in SAMP6 Mice by Inhibiting Oxidative Stress, Cellular Senescence, and the SASP
Wang, S., Heng, K., Song, X., Zhai, J., Zhang, H., & Geng, Q. (2023) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202300330 · Cited by 18
Nanotechnology for vision restoration
Lanzani, G., Chiaravalli, G., Colombo, E., Manfredi, G., Marco, S. D., Vurro, V., & Benfenati, F. (2024) · Nature Reviews Bioengineering · doi:10.1038/s44222-024-00210-4 · Cited by 18
Endothelial protein C receptor promotes retinal neovascularization through heme catabolism
Song, H., Li, Q. X., Gui, X., Fang, Z., Zhou, W. S., Wang, M., Jiang, Y., Geng, A., Shen, X. P., Liu, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-56810-0 · Cited by 21
Corticosteroids reduce pathological angiogenesis yet compromise reparative vascular remodeling in a model of retinopathy
Hata, M., Hata, M., Dejda, A., Pilon, F., Diaz-Marin, R., Fournier, F., Joyal, J., Cagnone, G., Ochi, Y., Crespo‐Garcia, S., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2411640121 · Cited by 17
Self-citation
The Role of Endothelial Senescence in the Pathogenesis of Diabetic Retinopathy
Gandhi, M., Haider, S., Chang, H. Z. Y., & Kazlauskas, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26115211 · Cited by 17
Aging in Ocular Blood Vessels: Molecular Insights and the Role of Oxidative Stress
Cui, X., Buonfiglio, F., Pfeiffer, N., & Gericke, A. (2024) · Biomedicines · doi:10.3390/biomedicines12040817 · Cited by 16
TRIM25 inhibition attenuates inflammation, senescence, and oxidative stress in microvascular endothelial cells induced by hyperglycemia
Sun, D., Li, S., Chen, S., Zhang, S., Gu, Q., Shen, Y., Fang, W., & Wang, N. (2023) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-023-06160-8 · Cited by 15
The role of microRNAs in the pathophysiology of the aging eye
Tamaddon, M., Fazel, M., Rezaee, D., Khalilzad, M. A., Majidpoor, J., Ahmadieh, H., Fattahi, M.-D., Namakin, K., Suri, F., & Najafi, S. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102805 · Cited by 14
Topical application of a BCL-2 inhibitor ameliorates imiquimod-induced psoriasiform dermatitis by eliminating senescent cells
Zhu, H., Jiang, J., Yang, M., Zhao, M., He, Z., Tang, C., Song, C., Zhao, M., Akbar, A. N., Reddy, V. R., et al. (2024) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2024.06.002 · Cited by 15
Mechanisms of cellular senescence-induced vascular aging: evidence of senotherapeutic strategies
Mahoney, S. A., Bloom, S. I., Seals, D. R., Donato, A. J., Rossman, M. J., & Clayton, Z. S. (2025) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2024.31 · Cited by 15
Nano-PROTACs for precision medicine: engineering strategies for enhanced targeting and potency
Yang, X., Wang, D., Li, C., Zhang, Y., Yang, J., Liu, M., Xing, D., Jiang, W., Xu, S., & Wang, C. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03985-9 · Cited by 13
HIF1α-dependent hypoxia response in myeloid cells requires IRE1α
Mawambo, G., Oubaha, M., Ichiyama, Y., Blot, G., Crespo‐Garcia, S., Dejda, A., Binet, F., Diaz-Marin, R., Sawchyn, C., Sergeev, M., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02793-y · Cited by 13
Self-citation
Connecting epigenetics and inflammation in vascular senescence: state of the art, biomarkers and senotherapeutics
Fraile‐Μartinez, O., León-Oliva, D. D., Boaru, D. L., Castro-Martinez, P. D., Montero, C. G., Barrena-Blázquez, S., García-García, J., García‐Honduvilla, N., Álvarez‐Mon, M., López-González, L., et al. (2024) · Frontiers in Genetics · doi:10.3389/fgene.2024.1345459 · Cited by 15
New Insights into the Role of Cellular Senescence and Its Therapeutic Implications in Ocular Diseases
Wu, J., Liu, X., Liu, Y., Su, W., & Zhuo, Y. (2025) · Bioengineering · doi:10.3390/bioengineering12060563 · Cited by 14
New insights of potential biomarkers in diabetic retinopathy: integrated multi-omic analyses
Wang, X., Liu, W., Zheng, X., & Yang, M. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1595207 · Cited by 14
Senescent Cells: Dual Implications on the Retinal Vascular System
Habibi-Kavashkohie, M. R., Scorza, T., & Oubaha, M. (2023) · Cells · doi:10.3390/cells12192341 · Cited by 12
Liraglutide improves senescence and ameliorating diabetic sarcopenia via the YAP-TAZ pathway
Xu, Q., Qiu, X., Di, H., Li, Z., Liu, Z., & Liu, K. (2025) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2025.108975 · Cited by 14
Long-term senolytic therapy with Dasatinib and Quercetin alleviates lipofuscin-dependent retinal degeneration in mice
Yang, B., Yang, K., Xi, R., Li, S., Chen, J., & Wu, Y. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103716 · Cited by 12
RNA-Seq Provides Insights into VEGF-Induced Signaling in Human Retinal Microvascular Endothelial Cells: Implications in Retinopathy of Prematurity
Ramshekar, A., Bretz, C. A., & Hartnett, M. E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137354 · Cited by 11
A galactose-tethered tetraphenylethene prodrug mediated apoptosis of senescent cells for osteoporosis treatment
Gao, X., Hu, Y., Zhang, Y., Huang, Y., Zhang, G., Zhang, X., Zhou, Y., & Zhang, D. (2025) · Science Advances · doi:10.1126/sciadv.adr2833 · Cited by 11
Emerging approaches in keloid scar healing: The synergistic role of nanoparticles and phytochemicals
Mercy, D. J., Girigoswami, K., & Girigoswami, A. (2025) · Chemical Engineering Journal · doi:10.1016/j.cej.2025.168048 · Cited by 11
Cellular senescence in pathologic retinal angiogenesis
Fu, Z., & Smith, L. E. H. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.03.010 · Cited by 11
Aging microvasculature: Effects on immune cell trafficking and inflammatory diseases
Reglero-Real, N., Rolas, L., & Nourshargh, S. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20242154 · Cited by 11
Monocyte-derived exosomal periostin driven by histone lactylation contributes to retinal neovascularization
Shen, W., Nie, Z., Wang, M., Zhang, H., Liu, Y., Zhu, H., Zhou, W., Zhang, L., Zhao, M., Zeng, H., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2501704122 · Cited by 10
Cholesterol Accumulation Promotes Photoreceptor Senescence and Retinal Degeneration
Terao, R., Sohn, B. S., Yamamoto, T., Lee, T. J., Colasanti, J. J., Pfeifer, C. W., Lin, J. B., Santeford, A. C., Yamaguchi, S., Yoshida, M., et al. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.10.29 · Cited by 11
The Ercc1−/Δ mouse model of XFE progeroid syndrome undergoes accelerated retinal degeneration
Narasimhan, A., Min, S.-H., Johnson, L. L., Roehrich, H., Cho, W., Her, T. K., Windschitl, C., O'Kelly, R. D., Angelini, L. A., Yousefzadeh, M. J., et al. (2024) · Aging Cell · doi:10.1111/acel.14419 · Cited by 10
SenMayo transcriptomic senescence panel highlights glial cells in the ageing mouse and human retina
Suresh, S., Karthik, G., Ouyang, J. F., Chrysostomou, V., Tang, S. A., Petretto, E. G., Crowston, J. G., & Bell, K. C. (2024) · npj Aging · doi:10.1038/s41514-024-00187-9 · Cited by 10
Modulation of senescent Lepr+ skeletal stem cells via suppression of leptin-induced STAT3‒FGF7 axis activation alleviates abnormal subchondral bone remodeling and osteoarthritis progression
Yu, F., Yin, B.-F., Liu, M., Zhang, W., Zhao, Z., Wang, L., Li, X., Li, P., Li, Z., Xu, R.-X., et al. (2025) · Stem Cell Research & Therapy · doi:10.1186/s13287-025-04342-1 · Cited by 9
The Destructive Cycle in Bronchopulmonary Dysplasia: The Rationale for Systems Pharmacology Therapeutics
Teng, M. F., Wu, T.-J., Pritchard, K. A., Day, B. W., Naylor, S., & Teng, R. (2025) · Antioxidants · doi:10.3390/antiox14070844 · Cited by 9
Unveiling the link: aging and its impact on ocular diseases
Wang, K., Xie, Y., Lin, Y., Zhu, R., Gao, T., Han, Z., Yang, Z., Jiang, X., Chen, H., Wu, Z., et al. (2025) · Experimental Eye Research · doi:10.1016/j.exer.2025.110551 · Cited by 12
Unraveling the meta-hallmarks between senescent and tumor cells: A new perspective for senolytic drug discovery
Liu, W., Fan, B., Fang, T., Li, H., Zhang, J., Liu, B., & Liu, Z. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.08.010 · Cited by 10
The Role of Galectin-3 in Retinal Degeneration and Other Ocular Diseases: A Potential Novel Biomarker and Therapeutic Target
Zhou, Z., Feng, Z., Sun, X., Wang, Y., & Dou, G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115516 · Cited by 9
Senescent retinal pigment epithelial cells promote angiogenesis in choroidal neovascularization via the TAK1/p38 MAPK pathway
Wang, Y., Ma, H., Yang, Q., Chen, K., Ye, H., Wang, X., Xia, J., Chen, X., Wang, X., Ye, S., et al. (2025) · Experimental Eye Research · doi:10.1016/j.exer.2025.110232 · Cited by 8
Insights into the therapeutic strategies for aging and aging-associated diseases
Dong, R., Wu, Q., Kan, J., Fu, C., Sorrentino, V., Chow, A., Lei, Y., Wu, D., Xu, Z., Du, J., et al. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02662-z · Cited by 12

Authors: Crespo-Garcia, S., Tsuruda, P. R., Dejda, A., Ryan, R. D., Fournier, F., Chaney, S. Y., Pilon, F., Dogan, T., Cagnone, G., Patel, P., Buscarlet, M., Dasgupta, S., Girouard, G., Rao, S. R., Wilson, A. M., O’Brien, R., Juneau, R., Guber, V., Dubrac, A., Beausejour, C., Armstrong, S., Mallette, F. A., Yohn, C. B., Joyal, J.-S., Marquess, D., Beltran, P. J., & Sapieha, P.
Affiliations: Unity Biotechnology (United States) (US)
Hôpital Maisonneuve-Rosemont (CA)
Centre Hospitalier Universitaire Sainte-Justine (CA)
Corresponding author: Tsuruda, Pamela R.
Sapieha, Przemyslaw
ORCID: Dejda, Agnieszka
Chaney, Shawnta Y.
Buscarlet, Manuel
Dasgupta, Sonali
Wilson, Ariel M.
Juneau, Rachel
Guber, Vera
Dubrac, Alexandre
Beausejour, Christian
Yohn, Christopher B.
Beltran, Pedro J.
Sapieha, Przemyslaw
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2021-04
Volume: 33
Issue: 4
Pages: 818-832.e7
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2021.01.011
OpenAlex: W3126392088
Cited by: 182
References: 81
Citations by year: 2026: 21 · 2025: 55 · 2024: 44 · 2023: 30 · 2022: 28 · 2021: 4
FWCI: 17.10
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 370 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: Université de Montréal
Canadian Diabetes Association (DI-3-18-5444-PS)
Canadian Institutes of Health Research (148460)
Fonds de Recherche du Québec - Santé
Canada Research Chairs
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords: pathological angiogenesis, diabetic retinopathy, cellular senescence, BCL-XL inhibition, senolysis, p16INK4a, neovascularization, endothelial cells, COL1A1, anti-apoptotic therapy
MeSH terms: Collagen Type I, alpha 1 Chain, Animals, Disease Models, Animal, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Neovascularization, Pathologic, Retinal Diseases, Tacrolimus, Cellular Senescence, Apoptosis, Cyclin-Dependent Kinase Inhibitor p16, Endothelial Cells, Flavonols, bcl-X Protein, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Pathological angiogenesis in retinopathy engages cellular senescence and is amenable to therapeutic elimination via BCL-xL inhibition

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks